| Project/Area Number |
12307057
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kanazawa University |
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Principal Investigator |
TSUJI Akira Kanazawa University, Pharmaceutical Sciences, Professor, 薬学部, 教授 (10019664)
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| Co-Investigator(Kenkyū-buntansha) |
SAI Yoshimichi Kanazawa University, Graduate School, Assistant Professor, 大学院・自然科学研究科, 助手 (40262589)
TAMAI Ikumi Tokyo University of Science, Pharmaceutical Sciences, Professor, 薬学部, 教授 (20155237)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥33,010,000 (Direct Cost: ¥29,500,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2002: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2001: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2000: ¥17,800,000 (Direct Cost: ¥17,800,000)
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| Keywords | transporter / absorption / drug disposition / systemic carintine deficiency / quantitative PCR / adenovirus vector / drug delivery / single nucleotide polymorphism / ポリロタキサン / ゼノバイオティクス / 血液脳関門 / 腎排泄 / H1アンタゴニスト / 輸送駆動力 / 生体防御 / ドラックデリバリー |
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| Research Abstract |
The author' s research on transporter-mediated pharmacokinetics focuses on the molecular functional characteristics of drug transporters including oligopeptide transporter, monocarboxylic acid transporter, anion transporter, organic cation transporters, organic cation/carnitine transporters (OCTNs) and the ATP-binding cassette transporters P-glycoprotein and MRP2. We have successfully demonstrated that the transporters play important roles in the influxes and/or effluxes of drugs in intestinal and renal epithelial cells, hepatocytes and brain capillary endothelial cells that form the blood-brain barrier. In the systemic carnitine deficiency (SCD) phenotype mouse model, juvenile visceral seatosis (jvs) mouse, a mutation in the OCTN2 gene was found. Furthermore, several types of mutation in human SCD patients were found, demonstrating that OCTN2 is a physiologically important carnitine transporter. OCTNs transport not only carnitine but also various organic cationic drugs in a sodium-independent manner. It is suggested that OCTNs are multifunctional transporters for the uptake of carnitine into tissue cells and at the same time for the elimination of intracellular organic cationic drugs. In this research term, novel cDNA of organic anion transporters i.e., OATP-B, OATP-D and OATP-E have been isolated and functionally characterized. Furthermore, single nucleotide polymorphism of OATP-B, OATP-C and OCTN2 in the Japanese population was analyzed. Although more data should be collected, such information will enable us to establish ultimate drug delivery system.
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